Hemoparasitic diseases are endemic in half of the world's livestock production areas and are the most important obstacle to the improvement of meat and milk production in developing nations. It is estimated that over 500 million cattle are at risk for babesiosis alone, and despite decades of research, there is still no effective, practical and safe means of immunizing livestock against this disease. The pathology of Babesia bovis infection in cattle is very similar to that caused by Plasmodium falciparum infection in humans, and is characterized by a generalized circulatory disturbance and sequestration of parasitized erythrocytes in the capillary beds, especially in the brain. The feasibility of developing a successful babesial vaccine is based on observations that recovery from an acute infection is associated with development of protective immunity, and that immunization with crude parasite extracts can induce partial protection against subsequent challenge. However, very little is known about the nature of protective antigens or the immune responses they evoke. Because cell-mediated immune effector mechanisms are crucial in obtaining protective immunity against other protozoan infections, we propose to study the interactions of Babesia-specific T cells and defined babesial protein antigens at the cellular and molecular level using bovine T cell clones and purified as well as recombinant antigens. The production of cytokines by T cells and macrophages following stimulation, and their effect on parasite viability, will also be examined. The intent of this proposal is to identify protective babesial antigens and immunologic effector mechanisms in cattle responsible for controlling babesiosis. Such information is useful for the rational design of a vaccine against this disease as well as others, such as malaria, caused by hemoprotozoan parasites.